Pharmacological Effects of .SIGMA.-Receptor Ligands. Functional characterization of a sigma receptor and its gene expression by haloperidol.

Nakata, Yoshihiro; Inoue, Atsuko; Sugita, Sayori

doi:10.1254/fpj.114.61

Cited by 1 publication

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“…Given the reported downregulation of brain sigma receptors (Inoue et al 2000;Itzhak and Stein 1991;Nakata et al 1999;Zambon et al 1997), we expected similar downregulation of haloperidol-related effects in our model. Only limited and indirect information is available about desensitization of cardiac sigma receptors.…”

Section: Discussionsupporting

confidence: 62%

Apparent desensitization of the effects of sigma receptor ligand haloperidol in isolated rat and guinea pig hearts after chronic treatmentThis article is one of a selection of papers published in a special issue on Advances in Cardiovascular Research.

Fialová

Križanová

Jarkovský

et al. 2009

Can. J. Physiol. Pharmacol.

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The supposed role of cardiac sigma receptors is fine tuning of contractility. Sigma receptors affect several ionic channels and hence their signaling is reflected by the electrophysiological properties of the heart. Numerous ligands of sigma receptors are known to prolong the QT interval and therefore cause a variety of arrhythmias, including severe ones. The effects of the prototypical sigma ligand haloperidol have been studied extensively in humans as well as in various animal models, primarily after acute administration. We examined the incidence of arrhythmias, changes in heart rate, and prolongation of QT interval in isolated Langendorff-perfused rat and guinea pig hearts after they were exposed to nanomolar concentrations of haloperidol. Hearts from both untreated (acute) and pretreated (chronic) animals were investigated. While QT prolongation and arrhythmias due to haloperidol administration were observed in untreated rat and guinea pig hearts, arrhythmias were completely prevented in both species of chronically treated animals. In treated guinea pigs, the results were generally less convincing. Since the hearts were exposed to nanomolar concentration of haloperidol, we conclude that our data may be explained by desensitization of sigma receptors.

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Section: Discussionsupporting

confidence: 62%